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To compare the efficacy and safety of postoperative topical loteprednol etabonate (LE) 0.5% with dexamethasone (DEX) 0.1% for the treatment of inflammation following pars plana vitrectomy (PPV).A total of 150 eyes of 150 patients who underwent transconjunctival PPV for various diagnoses were included in this prospective, randomized study. The patients were assigned into two groups as Group LE (n = 75) and Group DEX (n = 75). Intraocular inflammation, intraocular pressure (IOP), and the intensity of postoperative pain were compared between the groups.The mean IOP was higher in the patients treated with DEX (p 0.05). The need for anti-glaucoma medications was significantly lower in Group LE (5.3%) than in Group DEX (17.3%) (p = 0.020). Tyndall scores were less in Group DEX at postoperative Days 1 (p = 0.01) and 3 (p = 0.017). On Day 1, it was more likely for patients to have mild or moderate pain in Group LE (p 0.001). On Day 3, the number of the patients with no pain was higher in Group DEX (p = 0.005).Although DEX is more effective in the early postoperative days, LE appears to be as effective in controlling inflammatory response following PPV in the long-term. Topical LE is associated with less increase in the IOP and a lower need for anti-glaucoma medications.

The soft drug approach is successful in obtaining high local therapeutic efficacy without systemic adverse effects, because soft drugs are designed to be bioconverted to inactive form by hydrolytic enzymes in systemic circulation. However, there is little information about the exact nature of these metabolic enzymes. In this study, the human enzymes for biotransformation of soft drugs were investigated. Loteprednol etabonate (LE) and etiprednol dicloacetate (ED) were designed from Δ 1 -cortienic acid (Δ 1 -CA), the inactive metabolite of prednisolone, by introducing two labile ester bonds to restore the corticosteroidal activity. We found that LE and ED were mainly deactivated in human plasma rather than the liver. Inactive monoesters were produced, but the second hydrolysis to Δ 1 -CA was much slower. ED was hydrolyzed 10 times faster than LE in plasma ( t 1/2 = 1.35 ± 0.08, 12.07 ± 0.52 h respectively). Paraoxonase 1 that attached with high density lipoprotein (HDL) was found to be the major hydrolase for LE and ED in human plasma as demonstrated by enzyme inhibition and stimulation experiments and the hydrolysis in lipoproteins-rich plasma fractions. Human serum albumin (HSA) showed slight hydrolase activity against ED but not LE. LE was slowly hydrolyzed in liver (clearance: 0.21 ± 0.04 and 2.41 ± 0.13 ml/h/kg in liver and plasma, respectively) but ED wasn’t hydrolyzed at all, so LE has superior metabolism in two sites. The difficult diffusion of HDL into tissues from blood suggests the stable presence of LE at the administration site, while ED might be deactivated by its relatively rapid chemical hydrolysis and hydrolase activity of HSA, in the interstitial fluid of the administration tissue. Moreover, deactivation in plasma and strong protein binding (around 98%) minimize the adverse effects of LE and ED in the systemic circulation.

PURPOSE To report a case of successful intraocular pressure (IOP) reduction after a 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) using the iTrack catheter in a patient with steroid-induced glaucoma as a result of treatment of vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS Case report. RESULTS An 8-year-old male individual with a long-standing history of VKC, treated with topical steroids, developed elevated IOP and glaucoma in the right eye despite maximum topical glaucoma therapy. Reducing the steroid was not a viable option given the severity of VKC. A 360-degree GATT was successfully performed and IOP has been maintained off all glaucoma drops. CONCLUSIONS GATT is a viable option for steroid-induced glaucoma in the pediatric population. This obviates the need for riskier, more invasive conjunctival-based procedures.

Topical ophthalmic corticosteroids are of clinical benefit in the management of pain and inflammation after ocular surgery; however, their use can be associated with class-associated adverse events (AEs) and limited bioavailability. Selection of an appropriate topical corticosteroid depends on drug-specific variables such as AE profile, efficacy, potency, dosing, patient-specific administration needs, and formulation properties aimed at minimizing precorneal drug loss, increasing ocular surface drug residence time, and maximizing drug delivery to the anterior tissues. Recently, strategies for improving ocular penetration of ophthalmic formulations have included use of mucoadhesive formulations (ie, polycarbophil-containing gels) and drug particle size reduction, enabling faster drug dissolution and therefore increased bioavailability and penetration. Loteprednol etabonate (LE) is a carbon-20 ester corticosteroid developed through retrometabolic drug design with potent anti-inflammatory effects and a reduced propensity for eliciting corticosteroid class AEs. This drug has been formulated for topical ophthalmic use after surgery as 0.5% and 1% suspensions, a 0.5% ointment, and a 0.5% gel. Preclinical and clinical data for a new 0.38% LE gel will be reviewed demonstrating that reducing the drug particle size to the nanometer range in diameter provides effective ocular tissue penetration and resolution of pain and inflammation despite a reduced drug concentration (0.38%) and dosing frequency.

JD Sheppard,1 IP Singh21Department of Ophthalmology, Eastern Virginia Medical School, Norfolk, VA, USA; 2Department of Glaucoma, The Eye Centers of Racine & Kenosha, Racine, WI, USAPurpose: With the increasing use of minimally invasive surgical techniques for intraocular pressure (IOP) lowering in glaucoma patients, there is a need to examine best practices regarding the postoperative management of these patients. Corticosteroids, though effective in controlling postoperative ocular pain and inflammation, present distinct challenges in glaucoma surgery patients, as their use can be associated with IOP elevation. Loteprednol etabonate (LE) is an ocular corticosteroid designed to have an improved safety profile relative to other corticosteroids.Methods: We report here a representative selection of cases in which patients were successfully treated with LE ophthalmic gel 0.5% (LE gel) following a variety of minimally invasive glaucoma surgery (MIGS) procedures. Cases included patients undergoing various procedures including a Trabectome combined with cataract surgery; micro-stent surgery (iStent) combined with cataract surgery; supraciliary CyPass Micro-Stent placement combined with cataract surgery; Kahook Dual Blade goniotomy; and ab interno canaloplasty using the iTrack catheter.Observations: In all cases, use of LE gel during the postoperative period appeared effective and safe in reducing inflammation and controlling pain. No adverse events or IOP elevations were noted, even in those patients continuing use of LE gel past the postoperative period for longer than six months with documented follow-up. In two cases, patients with elevated IOP using either prednisolone or difluprednate postoperatively were switched to LE gel, with a subsequent reduction in IOP.Conclusions: This selection of cases involving patients undergoing MIGS suggests that LE gel may be an effective and safe option for treating postoperative inflammation and pain following such procedures with minimal to no effect on IOP or other negative sequalae.Keywords: loteprednol etabonate, minimally invasive glaucoma surgery, intraocular pressure, postoperative pain and inflammation, safety

Surgical trauma, and foreign material - such as sutures or implants or antigens during tissue transplantation - may cause inflammatory reactions. Inflammatory reactions after surgical interventions distant from the vascularised limbus and without opening of the anterior chamber of the eye are usually very muted, because of the corneal immune and angiogenic privilege. A milestone in the therapy and prophylaxis of inflammation after corneal surgery has been the use of topical glucocorticoids since the 1950s. When these are used, it is important to consider the cataractogenic effect of long-term use, the possibility of steroid-induced increase in intraocular pressure (so-called steroid response), the increased risk for microbial infection and the inhibition of epithelialisation. The available glucocorticoids differ in their ability to penetrate into the eye (prednisolone best), their immunosuppressive activity (dexamethasone best) and their ability to induce a steroid response (loteprednol etabonate and fluorometholone least). Preservative-free formulations are only available for dexamethasone. The different properties must be taken into account when choosing the "best" glucocorticoid: If there is a risk of delay in epithelialisation of the wound, topical steroids should be avoided or if necessary, phosphate- and preservative-free dexamethasone should be used with caution. If efficiency in the posterior cornea or in the anterior chamber is important, e.g. after penetrating keratoplasty, prednisolone acetate should be used. If a steroid response is known, loteprednol etabonate or fluorometholone should be used. When allogeneic tissue is transplanted, long-term topical glucocorticoid use over 24 months or longer is necessary. After high-risk keratoplasty with allogeneic donor tissue, supplemental systemic immunosuppressive therapy with calcineurin inhibitors or mycophenolate mofetil over 6 to 12 months is recommended.Nach Hornhautchirurgie kommt es durch das mechanische Trauma, durch Fremdkörper wie z. B. Nähte oder Implantate oder durch Antigene bei Gewebetransplantation zu entzündlichen Reaktionen. Nach chirurgischen Eingriffen mit Abstand zum vaskularisierten Limbus verlaufen diese aufgrund des Immunprivilegs und des angiogenen Privilegs der Hornhaut in aller Regel sehr gedämpft. Hauptpfeiler in der Therapie und Prophylaxe von Entzündungen nach Hornhautchirurgie sind topische Glukokortikoide. Bei der Anwendung müssen die kataraktogene Wirkung bei Langzeitnutzung, die Möglichkeit einer steroidbedingten Augeninnendruckerhöhung als sogenannte Steroidresponse, die Erhöhung der Infektanfälligkeit und die Hemmung einer Epithelialisierung berücksichtigt werden. Die verfügbaren Glukokortikoide unterscheiden sich in ihrer Fähigkeit zur Penetration in das Auge (Prednisolon am besten), ihrer immunsuppressiven Wirkung (Dexamethason am besten) und im Risiko der Induktion einer Steroidresponse (Loteprednoletabonat und Fluorometholon am geringsten). Die unterschiedlichen Eigenschaften müssen bei der Wahl des „richtigen“ Glukokortikoids berücksichtigt werden: Bei Gefahr einer Epithelialisierungsstörung sollten topische Steroide möglichst vermieden bzw., falls zwingend erforderlich, konservierungsmittelfreies und phosphatfreies Dexamethason (Dexapos COMOD

Purpose: To evaluate rheological properties, in vitro dissolution, and in vivo ocular pharmacokinetics of loteprednol etabonate (LE) (submicron) ophthalmic gel 0.38%. Methods: The viscosity of the LE gel 0.38% formulation was measured with a controlled stress rheometer. Dissolution kinetics were evaluated in a fixed-volume and flow-through assay. Rabbits received a single instillation of LE (submicron) gel 0.38% (both eyes), and concentrations of LE in ocular tissues were determined through 24 h by liquid chromatography with tandem mass spectrometry. Where indicated, comparators included micronized LE gel 0.38%, 0.5% (Lotemax® gel), and 0.75%. Results: LE (submicron) gel 0.38% exhibited shear-thinning characteristics similar to LE gel 0.5% with nearly identical yield stress. LE (submicron) gel 0.38% released 2.6-fold more LE into the dissolution medium than micronized LE gel 0.5% over 30 s in the fixed-volume dissolution assay, and submicron LE attained higher concentrations of dissolved LE than micronized LE gel 0.38% in the flow-through dissolution assay. In rabbits, the maximal concentration and area-under-the-curve over 24 h for LE in aqueous humor were 2.5- and 1.8-fold higher, respectively, for LE (submicron) gel 0.38% versus micronized LE gel 0.5% (both P

PURPOSE To study the effect of periocular steroid use on intraocular pressure (IOP). METHODS Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. RESULTS Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1-83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of

Background Allergic conjunctivitis (AC) is a disease of various agents that affects the physical and mental health of children. Although the most effective therapy has not been found so far, it is essential to explore the considerable therapeutic method. We compared the clinical efficacy of olopatadine, emedastine, loteprednol etabonate (LE), and vehicle for treating seasonal allergic conjunctivitis (SAC) in Chinese children. Methods Eighty cases of 160 eyes aged from 5 to 10 years with SAC were available and those subjects were randomly distributed into 4 groups. Both their eyes received olopatadine hydrochloride 0.1% twice a day, emedastine difumarate 0.05% twice a day, or LE 0.5% 4 times a day, respectively, whereas those of the control group received artificial tears (AT) 0.5% 3 times a day. This study was conducted successfully and the observations were collected before treatment and on day 8 (±1 day) and day 15 (±2 days) afterward. The principal measurement of efficacy was focused on the signs and symptoms of the subjects, evaluated before and after treatment, in addition to visual acuity (VA) and fundus oculi. Results On day 8 (±1 day) and day 15 (±2 days), all the antiallergic agents were found to be more effective than vehicle (p < 0.05) in terms of all the symptoms and signs. However, there was no statistical significance (p ≥ 0.05) shown among the treatment groups. There were no evident changes in VA and no clinically significant changes were observed in fundus oculi. Conclusion After the treatment, the efficacy presented a similar distribution among the trial groups.

A novel cationic nanoemulsified in-situ ophthalmic gel of loteprednol etabonate (LE) was developed to improve the permeability and retention time of formulations for overall improvement of drug’s ocular bioavability. Capryol 90 (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) was selected as formulation excipients to construct pseudoternary phase diagrams and nanoemulsion region was recognized from diagrams. Spontaneous emulsification method was used to manufacture LE nanoemulsion and it was optimized using 32 factorial design by considering the amount of oil and the ratio of surfactant to cosurfactant (Smix) as independent variables and evaluated for various physicochemical properties. Optimized NE was dispersed in Poloxamer 407 and 188 solution to form nanoemulsified sols that were predictable to transform into in-situ gels at corneal temperature. Drug pharmacokinetics of sterilized optimized in situ NE gel, NE-ISG2 [0.69% w/w Capryol 90, 0.99%w/w Smix (3:1), 13% Poloxamer 407,...

Purpose: Patients with absent iris crypts are the most challenging cases for performing laser peripheral iridotomy. This study was conducted on patients of primary angle closure disease belonging to this group to find out the difference in the quantum of energy and number of attempts required to achieve optimum peripheral iridotomy by sequentially using double frequency Nd:YAG and Nd:YAG laser versus Nd:YAG laser alone. Methods: Forty eyes of 40 patients of 35 years or more, with primary angle closure disease and absent iris crypts, in whom laser peripheral iridotomy (LPI) was indicated, were prospectively randomized into two groups. Patients in group one sequentially underwent double frequency Nd:YAG & Nd:YAG laser and group two underwent Nd:YAG laser alone. Follow up was done one hour, three hours, one day and one week post laser. Any rise of IOP of > 8 mmHg from base line or an absolute figure of 30 mmHg at any visit was considered significant. Post laser topical loteprednol etabonate 4 times per day for one week and pilocarpine nitrate 2% eye drops twice a day for five days were used in all cases. Statistical testing was conducted with the statistical package for the social science system (SPSS) version 17.0. Results: Group one had 3 male and 16 female patients whereas group two had 9 and 12 male and female patients respectively. Nd:YAG energy required in group one (n=19) was 48.79 ± 19.41 mJ and in group two (n=21) was 88.81 ± 37.36 mJ (p=

A reverse phase ultra-high performance liquid chromatography (RP-UHPLC) method was developed and validated for the simultaneous estimation of Loteprednoletabonate (LOTE) and Gatifloxacin (GAT) in pharmaceuticaldosage form. The separation was carried on zorbax eclipse plus column C18 (4.6 × 50 mm, 1.8 μ particle size) column with mobile phase (pH 6.0 withtriethylamine) containing Acetonitrile, Methanol and 0.02M potassiumdihydrogen phosphate in the ratio of 40:30:30 v/v/v with a flow rate of 0.7 mL/min and UV detection at 272 nm. The linearity was found to be in range of 15.34-46.03 μg/mL (R 2 = 0.999) and 24.94-74.81 μg/mL (R 2 = 0.999) for GAT and LOTE respectively. The method has shown good, consistent recoveries for GAT 98.88-101.24% and LOTE 98.42 - 100.94% respectively. The method was found to be accurate, precise, specific,robust and linear for the determination of GAT and LOTE in pharmaceutical dosage form.

Purpose: To compare the efficiency and ocular side-effect profile of topical loteprednol applied to one eye and topical dexamethasone applied to the other eye in the early period on the same patient who has subepithelial infiltrates (SEI).Methods: The patients who developed bilateral SEI following epidemic keratoconjunctivitis (EKC) were applied topical loteprednol on one eye (group 2) and topical dexamethasone on the other (group 1).Results: Decrease in the symptoms was faster in the dexamethasone group, but this difference between the groups was not statistically significant (p = 0.073). Both groups were found to have substantial recurrence. However, the difference between the groups was not statistically significant (p = 0.131).Conclusions: The study has found that in the treatment of SEI, which developed after EKC, statistically similar results can be obtained with loteprednol, which is known to have fewer adverse effects.

Purpose: To compare the efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T) ophthalmic suspensions in reducing select signs of blepharitis.Methods: Data were pooled from two studies (one from the USA; one from China) of adults (n = 627) with blepharokeratoconjunctivitis treated with LE/T or DM/T four times daily for 2 weeks (safety population). Efficacy analyses included 495 eyes (247 LE/T, 248 DM/T) with any baseline sign of blepharitis.Results: At Day 15, the least squares mean change from baseline in composite blepharitis severity was similar between LE/T (–2.86) and DM/T (–2.99) (90% CI for mean treatment difference: –0.35, 0.11). Intraocular pressure (IOP) increases ≥10 mmHg over baseline were reported for 1 US patient (DM/T group) and 19 Chinese patients (6 LE/T; 13 DM/T).Conclusions: LE/T was similarly effective in reducing the signs of blepharitis compared with DM/T, but demonstrated a better safety profile with respect to changes in IOP.

To improve the efficiency of topical ocular drug administration, we focused on development of a nanoparticles loaded contact lens to deliver the hydrophobic drug over a prolonged period of time. The cross-linked nanoparticles based on PCL (poly ε-caprolactone), 2-hydroxy ethyl methacrylate (HEMA), and poly ethylene glycol diacrylate (PEG-DA) were prepared by surfactant-free miniemulsion polymerization. The lens material was prepared through photopolymerization of HEMA and N-vinylpyrrolidone (NVP) using PEG-DA as the cross-linker. Effects of nanoparticles loading on critical contact lens properties such as transparency, water content, modulus and ion and oxygen permeabilities were studied. Nanoparticles and hydrogel showed high viability, indicating the absence of cytotoxicity and stimulatory effect. Drug release studies revealed that the hydrogel embedded with nanoparticles released the drug for a period of 12 days. The results of this study provide evidence that nanoparticles loaded hydrogels could be used for extended delivery of loteprednol etabonate and perhaps other drugs.

To compare the anti-inflammatory efficacy and safety of 0.5% loteprednol etabonate/0.3% tobramycin (LE/T) and 0.1% dexamethasone/0.3% tobramycin (DM/T) ophthalmic suspensions following strabismus surgery.The records of 40 patients who were treated with either LE/T or DM/T following strabismus surgery were retrospectively reviewed. The recorded signs and symptoms of inflammation and intraocular pressure of the patients at 1 day, 1 week, and 3 weeks after the surgery were evaluated and compared between the groups.In both groups, reduced inflammation was noted during the follow-up visits. There was no statistically significant difference between the LE/T and DM/T groups with regard to the postoperative scores or measurements, including discomfort, chemosis, secretion, conjunctival hyperemia, and conjunctival gap size (p0.05), during the follow-up visits. Allergic reactions to the medications were not reported in any patient. Intraocular pressures were within normal limits in both groups.LE/T was found to be as effective as DM/T in reducing inflammation after strabismus surgery. LE/T, as a new-generation steroid combination product, could be used as a safe and effective anti-inflammatory agent for the treatment of inflammation following strabismus surgery.Şaşılık cerrahisi sonrası loteprednol etabonat %0,5/tobramisin %0,3 (LE/T) ve deksametazon %0,1/tobramisin %0,3 (DM/T) oftalmik solüsyonlarının antiinflamatuar etkinlik ve güvenliğinin karşılaştırılması.Şaşılık cerrahisi sonrası, LE/T veya DM/T ile tedavi uygulanmış 40 hastanın kayıtları retrospektif olarak gözden geçirildi. Hastaların cerrahi sonrası 1. gün, 1. ve 3. haftalarda kaydedilen göz içi basınçları, enflamasyona ait semptom ve bulguları değerlendirildi ve gruplar arasında karşılaştırma yapıldı.Her iki grupta, takiplerde enflamasyonun azaldığı değerlendirildi. Operasyon sonrası, LE/T ve DM/T grupları arasında, rahatsızlık hissi, kemozis, sekresyon, konjonktival hiperemi skorları ve konjonktiva açıklık değerleri açısından istatistiki olarak anlamlı bir fark tespit edilmedi. (p0.05) Hastaların hiçbirisinde alerjik reaksiyon rapor edilmemişti. Göz içi basınçları her iki grupta da normal sınırlar içerisindeydi.LE/T’nin, DM/T kadar şaşılık cerrahisi sonrası inflamasyonun azaltmasında etkin olduğu; yeni jenerasyon steroid kombinasyon ürünü olarak, güvenli ve etkili olarak kullanılabileceği kanaatine varıldı.

Loteprednol etabonate ophthalmic gel 0.38% (Lotemax

Excipients from different sources may lead to significant differences in the performance of drug products, posing challenges in product quality control. A previous report showed that the drug release rates from ophthalmic ointments were affected by source variation of white petrolatum. To understand the physicochemical properties including the microstructure of white petrolatum and the impact of this on the performance of finished products, the following were investigated: rheological properties, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), as well as structural characteristics (polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS)). The rheological parameters may be indicative of the drug release rate of the finished ophthalmic ointments when using a process involving hot-melting with immediate cooling. The white petrolatum from the four different sources also showed different thermal behavior. According to SAXS and WAXS, all of the petrolatum showed semi-crystalline behavior with different extents of crystallinity (from 9.5% to 16.9%). The crystalline domains of the petrolatum are ordered in an orthorhombic structure forming lamellar sheets with a periodicity from 9.1 nm to 9.9 nm. An in-depth understanding of the semi-crystalline structure was obtained and it provided valuable information for formulation optimization and characterization of petrolatum-based products.

To better understand the nature of periocular dermatitis (PD) patient presentation, treatment, time-to-cure, and referral pattern for allergy testing in an ophthalmic academic center.A retrospective chart review of 344 patients diagnosed with PD between January 1, 2000 and November 30, 2016 at the Edward S. Harkness Eye Institute was performed. Eighty patients were eligible for the study. The primary endpoint was the time-to-cure. Cox proportional hazards regression was performed to assess if there was a significant difference between time-to-cure in patients treated with: 1) combination topical steroid/antibiotic (n = 6) vs. topical steroid alone (n = 40) and 2) combination topical steroid and oral antihistamine (n = 5) vs. topical steroid alone (n = 40).The median age of eligible patients was 57.69 years old, 66.25% of patients were female, and 41.25% had a history of atopy. Seven patients in total were referred for allergy testing. A significant difference was found in likelihood of cure when comparing combination topical steroid and oral antihistamine versus topical steroid alone, adjusting for age and gender (aHR = 3.97, 95% CI: 1.40-11.25). No significance was found when comparing combination topical steroid/antibiotic versus topical steroid alone (aHR = 1.96, 95% CI: 0.72-5.27).Patients treated with topical steroid and oral antihistamine were approximately 4 times more likely to experience cure in comparison to patients treated with topical steroids alone. While the majority of patients were not referred for formal allergy testing, this would likely be of benefit.

To evaluate 0.1% diclofenac sodium as an adjunctive therapy with loteprednol etabonate on postoperative inflammation in the anterior chamber and on foveal and parafoveal retinal thickness.Eighty eyes eligible for phacoemulsification were enrolled in a randomized clinical trial. Patients in group I (N = 40) received anti-inflammatory treatment consisting of 0.1% diclofenac with 0.5% loteprednol; group II (N = 40) patients received 0.5% loteprednol alone. Best corrected visual acuity and intraocular pressure were measured, and laser flarephotometry was done. Foveal and parafoveal thickness were assessed by optical coherence tomography. Results: Median flare values decreased more rapidly in group I at 7 and 14 days (7.9 and 7.4 ph/ms, respectively) than in group II (13.7 and 11.8 ph/ms, respectively; p0.0001). Group II had significantly increased parafoveal thickness at 14 and 42 days (median 285.59 μm, p = 0.001 and 288.38 μm, p0.001, respectively). Parafoveal thickness differed significantly between groups at 14 and 42 days (p = 0.0085, p = 0.0004, respectively).Eyes treated with both diclofenac sodium and loteprednol etabonate showed less inflammatory response and were less likely to develop foveal and parafoveal thickening than those treated with steroid only.

Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ

To compare intraocular pressure (IOP) elevation and graft rejection with loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty (DMEK).In this prospective, evaluator-masked trial, 167 patients were randomized to loteprednol or prednisolone in a 1:1 ratio 1 month after DMEK; 66 fellow eyes were enrolled and assigned to the opposite treatment. Dosing was 4 times daily for 2 months, thrice daily for 1 month, twice daily for 1 month, and once daily for 7 months. The main outcomes were IOP elevation (defined as IOP ≥ 24 mm Hg or an increase of ≥10 mm Hg over the baseline preoperative level) and immunologic rejection episodes, assessed by Kaplan-Meier survival analysis and proportional hazards modeling.A total of 233 eyes were assigned to treatment. Loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution were equally effective in preventing immunologic rejection episodes; none (0%) occurred with either treatment (P = 1). IOP elevation was twice as likely in the prednisolone-treated eyes (relative risk = 2.3, 95% confidence interval: 1.2-4.5, P = 0.016). The proportion with IOP elevation was 25% in prednisolone-treated eyes versus 11% in loteprednol-treated eyes (P = 0.013). In 66 subjects with fellow eyes assigned to opposite treatments, an IOP increase of ≥10 mm Hg was significantly more likely in the prednisolone-treated eye (P = 0.031).Loteprednol etabonate 0.5% gel was as effective as prednisolone acetate 1% solution in preventing immunologic graft rejection episodes after DMEK and was significantly less likely to cause IOP elevation.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01853696.

This retrospective study was performed to analyze the long-term outcome of topical corticosteroid treatment for severe dry eye associated with Sjogren's syndrome (SS). Patients who had severe dry eye associated with SS were topically treated with loteprednol etabonate 0.5% (group A, n=66) or fluorometholone 0.1% (group B, n=67) twice daily and were followed up for 2 years. Visual acuity (VA), intraocular pressure (IOP), Schirmer test, tear film breakup time (BUT), keratoepitheliopathy, and symptom scores were measured at baseline and 6, 12, 18, and 24 months after treatment. VA and IOP were not changed significantly during follow-up in either group. Schirmer test results, keratoepitheliopathy, and symptom scores at 6, 12, 18, and 24 months (p

To compare loteprednol etabonate 0.5%/tobramycin 0.3% (Zylet(®)) with dexamethasone 0.1%/tobramycin 0.3% (Tobradex(®)) in terms of the epithelial healing time, postoperative visual acuity, corneal haziness score, and intraocular pressure (IOP) in postoperative treatment after photorefractive keratectomy (PRK).This prospective, randomized, double-masked (participants and assessors blinded) controlled study included 32 patients who underwent PRK. The patients were allocated equally into 2 groups by block randomization to receive either loteprednol etabonate (Lot) or dexamethasone (Dex) for 1 month after the surgery. The epithelial healing time, uncorrected visual acuity (UCVA), corneal haziness score, and IOP were evaluated at 1 week, 1 month, and 3 months.The corneal epithelium was healed within 3 days in both groups; however, the epithelium was closed on the second day in 3 cases in the Lot group compared with 1 case in the Dex group. No significant differences were found for UCVA at 1 and 3 months (Fisher exact test, P0.01). Similarly, there was no statistically significant difference in corneal haziness scores between the 2 groups at 1 and 3 months (Mann-Whitney U test, P0.05). The number of patients experiencing significantly increased IOP (≥5 mmHg) from baseline at any visit for the Lot group (1/16 patients) was fewer than for the Dex group (3/16 patients).Loteprednol etabonate was effective in postoperative PRK management and was significantly less likely to produce elevations in IOP than was dexamethasone.

Prevention and management of postoperative ocular inflammation with corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) have been evaluated in several randomised controlled trials (RCTs). However, neither consensus regarding the efficacies of different regimens nor established guidelines are currently available. This has resulted in different practice patterns throughout the world. A systematic literature review found that for the management of postcataract inflammation nepafenac produced a positive outcome in three of three RCTs (3/3), as did ketorolac (1/1), bromfenac (7/7), loteprednol (3/3) and difluprednate (6/6), but not flurbiprofen (0/1). A single study found that betamethasone produced inconclusive results after retinal detachment (RD) surgery; ketorolac was effective (1/1) after vitrectomy, but triamcinolone was ineffective (0/1) after trabeculectomy. A two-round Delphi survey asked 28 international experts to rate both the inflammatory potential of different eye surgeries and their agreement with different treatment protocols. They rated trabeculectomy, RD surgery and combined phacovitrectomy as more inflammatory than cataract surgery. Vitrectomies for macular hole or epiretinal membrane were not deemed more inflammatory than cataract surgery. For trabeculectomy, they preferred to treat longer than for cataract surgery (NSAID + corticosteroid three times a day for 2 months vs 1 month). For vitrectomy alone, RD surgery and combined phacovitrectomy, the panel preferred the same treatment as for cataract surgery (NSAID + corticosteroid three times a day for 1 month). The discrepancy between preferred treatment and perception of the eye's inflammatory status by the experts for RD and combined vitreoretinal surgeries highlights the need for RCTs to establish treatment guidelines.

BACKGROUND Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. METHODS The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. RESULTS The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. CONCLUSION The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours.

ObjectivesLoteprednol etabonate (LE) is the first, highly successful soft corticosteroid (SC) designed using the ‘inactive metabolite’ approach, starting with ∆1-cortienic acid (d-CA). The next generation of SCs based on d-CA was etiprednol dicloacetate (ED). The 17α-dichloroacetyl function serves both as a unique pharmacophore and as the source of the molecule's softness. Highly potent SCs were designed based on a combination of ED and LE, introducing 6, 9 and 16 substituents in the molecule.MethodsThe new 6α, 9α, 16α and β 17α-dichloroacetyl 17β-esters were synthesized from the correspondingly substituted ∆1-cortienic acids. The anti-inflammatory activity was assessed using LPS-induced TNF α-release under various conditions to determine intrinsic activity vs. systemic biological stability. In vivo anti-inflammatory activity was studied in the widely used ovalbumin-sensitized and ovalbumin-challenged Brown Norway rat model.Key findingsThe 6α or 9α-fluoro substitution produced highly potent corticosteroids, but the 17α-dichloroacetyl substituent provided ‘softness’ in all cases. Local application of these steroids will significantly reduce systemic activity, due to the facile hydrolytic deactivation of these molecules.ConclusionsA 17α-dichloroacetyl derivative of fluticasone (FLU) is highly potent but much safer than the currently used propionate or furoate ester.

To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery.Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively.Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit.The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.

Background Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia. Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation. Although both topical and systemic treatments are used to treat people with BKC, this Cochrane review focuses on topical treatments. Objectives To assess and compare data on the efficacy and safety of topical treatments (including antibiotics, steroids, immunosuppressants and lubricants), alone or in combination, for BKC in children from birth to 16 years. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE ( January 1946 to 11 July 2016), Embase (January 1980 to 11 July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We searched the reference lists of identified reports and the Science Citation Index to identify any additional reports of studies that met the inclusion criteria. Selection criteria We searched for randomised controlled trials that involved topical treatments in children up to 16 years of age with a clinical diagnosis of BKC. We planned to include studies that evaluated a single topical medication versus placebo, a combination of treatments versus placebo, and those that compared two or multiple active treatments. We planned to include studies in which participants received additional treatments, such as oral antibiotics, oral anti-inflammatories, warm lid compresses and lid margin cleaning. Data collection and analysis Two review authors independently screened the results of the literature search (titles and abstracts) to identify studies that met the inclusion criteria of the review and applied standards as expected for Cochrane reviews. We graded the certainty of the evidence using GRADE. Main results We included one study from the USA that met the inclusion criteria. In the study, 137 children aged zero to six years old with blepharoconjunctivitis were randomised to treatment in one of four trial arms (loteprednol etabonate/tobramycin combination, loteprednol etabonate alone, tobramycin alone or placebo) for 15 days, with assessments on days 1, 3, 7 and 15. We judged the study to be at high risk of attrition bias and bias due to selective outcome reporting. The study did not report the number of children with improvement in symptoms nor with total or partial success as measured by changes in clinical symptoms. All children showed a reduction in blepharoconjunctivitis grade score, but there was no evidence of important differences between groups. Visual acuity was not fully reported but the authors stated that there was no change in visual acuity in any of the treatment groups. The study reported ocular and non ocular adverse events but was underpowered to detect differences between the groups. Ocular adverse events were as follows: loteprednol/tobramycin 1/34 (eye pain); loteprednol 4/35 (eye pain, conjunctivitis, eye discharge, eye inflammation); tobramycin 0/34; placebo (vehicle) 0/34. The evidence was limited for all these outcomes and we judged it to be very low certainty. There was no information on clinical signs (aside from grade score), disease progression or quality of life. Authors' conclusions There is no high-quality evidence of the safety and efficacy of topical treatments for BKC, which resulted in uncertainty about the indications and effectiveness of topical treatment. Clinical trials are required to test efficacy and safety of current and any future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.

The purpose of the study was to determine the concentrations of FlarexDrug concentrations of shaken versus unshaken Flarex and Lotemax were determined over a 20-day simulated tapered course in our institutional laboratory. Collected samples were analyzed by reversed-phase high-performance liquid chromatography with photodiode array detection at 240 nm.Flarex had a mean concentration of 93.7% of the declared concentration when shaken and 7.25% when not shaken. The difference between these groups was statistically significant (P = 0.0001). Lotemax had a mean concentration of 96.74% of the declared concentration when shaken and a mean concentration of 98.97% when not shaken. The difference between these groups was not statistically significant (P = 0.194).Flarex maintains dose uniformity when shaken. When not shaken, it has poor dose uniformity. Lotemax was consistent whether shaken or not in our study and can be considered to eliminate the variability of poor patient compliance with shaking. The manufacturers of both drugs recommend shaking before application.

Purpose: The aim of this study was to compare the ocular hypertensive effect of the commercially available Betamethasone, Fluorometholone in Iran and Loteprednol Etabonate in patients undergoing keratorefractive surgery. Methods: In this prospective randomized clinical trial, 300 eyes of 150 patients were included, and patients were randomly assigned to 3 groups and used one of the 3 steroid drops (Betamethasone 0.1%, Fluorometholone 0.1%, and Loteprednol Etabonate 0.5%) after myopic photorefractive keratectomy (PRK). Intraocular pressure (IOP) was measured 2, 4, and 6 weeks post-surgery. Twenty-two mmHg was set as the threshold IOP for starting anti-glaucoma medication and tapering steroid drops. Results: Of 300 eyes from 150 patients over the first 6 postoperative weeks, 2 eyes in Fluorometholone group (2%), 12 eyes in Betamethasone group (12%), and 16 eyes in Loteprednol group (16%) had IOP equal or more than 22 mmHg. Analysis of variance (ANOVA) test showed that the rise in IOP was significantly different between groups in the 2nd and 4th (P ≤ 0.001) postoperative weeks but not at 6th week (P = 0.230). An IOP rise equal or more than 10 mmHg was detected in 13 and 15 eyes in Betamethasone and Loteprednol groups, respectively. None of the eyes in Fluorometholone group had such an IOP rise. Conclusions: Loteprednol and Fluorometholone were associated with the most and least increase in IOP, respectively. The highest pressures were detected 4 weeks after surgery in the Betamethasone and Loteprednol groups and 6 weeks after surgery in the Fluorometholone group. Fluorometholone was the safest among the three examined steroid drops in terms of IOP rise. Keywords: Steroid induced glaucoma, Loteprednol etabonate, Keratorefractive surgery, Photorefractive keratectomy

The investigation of semisolid ophthalmic ointments is challenging due to their complex physicochemical properties and the unique anatomy of the human eye. Using Lotemax® as a model ophthalmic ointment, three different manufacturing processes and two excipient sources (Fisher® (OWP) and Fougera® (NWP)) were used to prepare loteprednol etabonate ointments that were qualitatively and quantitatively the same across the manufactured formulations. Physicochemical properties including drug content and uniformity, particle size and distribution, as well as rheological parameters (onset point, crossover modulus, storage modulus and Power law consistency index) were investigated. In addition, USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the ophthalmic ointments. Both manufacturing processes and excipient sources had a significant influence on the physicochemical attributes and the in vitro drug release profiles of the prepared ointments. Ointments prepared via the hot melt processes exhibited higher rheological parameters and lower drug release rates compared to ointments prepared without hot melting. Ointments prepared with OWP demonstrated higher rheological parameters and lower in vitro drug release rates compared to ointments prepared with NWP. A strong correlation between the rheological parameters and in vitro drug release rate was shown using logarithmic linear regression. This correlation may be useful in predicting in vitro drug release from measured physicochemical properties, and identifying the critical quality attributes during the development of ointment formulations.

Objective: The purpose of this work was to evaluate the effect of loteprednol etabonate (LE) before the initiation of topical cyclosporine A (tCsA) therapy in patients with mild-to-moderate dry eye disease. Prospective, multicenter randomized double-masked parallel group clinical study (NCT00407043). Methods: Hundred and eighteen patients with dry eye disease were randomized to receive either LE and tCsA (n=61) or artificial tears (AT) and tCsA (n=57). Hundred and twelve patients completed the study (LE: n=57, AT: n=55) and are included in the data analysis. Patients selfadministered either LE or AT for 2 weeks 4 times per day, followed by tCsA twice per day accompanied by either LE twice per day or AT twice per day for an additional 6 weeks of treatment. Primary outcome measures included the Ocular Surface Disease Index (OSDI) questionnaire, the Likert scale using standardized facial expressions, lissamine green staining, fluorescein staining, and the Schirmer test. Additional measures included global self-assessment, and safety outcomes included slitlamp examination, intraocular pressure, and assessment of visual acuity. Results: Loteprednol etabonate pretreatment significantly reduced tCsA stinging (P,0.05). Both groups showed significantly improved OSDI scores at the 14-, 30-, and 60-day visits. Loteprednol etabonate showed significantly more OSDI improvement than AT. Both pretreatment strategies improved global self-assessment scores, Schirmer test, fluorescein staining, lissamine staining, and adjunctive AT use. Loteprednol etabonate showed superior improvement in Schirmer test, fluorescein staining, and lissamine staining. Intraocular pressure did not increase in either group. Conclusions: Loteprednol etabonate induction therapy 2 weeks before the initiation of long-term tCsA treatment for chronic dry eye disease provides more rapid relief of dry eye signs and symptoms with greater efficacy than tCsA and AT alone.